Is CNTNAP1 p.Asp109= (c.327C>T) pathogenic?

CNTNAP1 p.Asp109= (c.327C>T) is classified Benign/Likely benign in CNTNAP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-04). Low-frequency (popmax 1.33%, afr); Associated with lethal congenital contracture syndrome 7.

What condition is associated with CNTNAP1 p.Asp109= (c.327C>T)?

CNTNAP1 p.Asp109= (c.327C>T) is associated with lethal congenital contracture syndrome 7, neuropathy, congenital hypomyelinating, 3 (ClinVar).

How common is CNTNAP1 p.Asp109= (c.327C>T) in the general population?

CNTNAP1 p.Asp109= (c.327C>T) is low-frequency (popmax 1.33%, afr) (gnomAD).

CNTNAP1 p.Asp109=

c.327C>T · rs115552583 · VCV781302

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.33%, afr)

Conditions

lethal congenital contracture syndrome 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 0.41, phastCons 1
Overall
CADD	12.95	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.33% African / African-American · 1,001/75,058 alleles

Filtering AF 1.26% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.24%

Overall 0.0682% 1,101/1,614,016 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.33%	75
Remaining individualsnot grpmax-eligible	0.0848%	1,179
Admixed American	0.0633%	1,579
Middle Eastern	0.0495%	2,019
South Asian	0.0022%	45,541
European (non-Finnish)	0.000339%	294,995

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CNTNAP1
Protein: p.Asp109=
Coding: c.327C>T
MANE Select: NM_003632
dbSNP: rs115552583
Type: single nucleotide variant
Location: chr17:42684193 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51
Residue 109: a disulfide bond; the f5/8 type c domain

Full CNTNAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

lethal congenital contracture syndrome 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuropathy, congenital hypomyelinating, 3

Similar variants

CNTNAP1 p.Arg1121Ter Pathogenic ★★ same condition
CNTNAP1 p.Arg697Ter Pathogenic/Likely pathogenic ★★ same condition
CNTNAP1 p.Arg835Ter Pathogenic ★★ same condition
CNTNAP1 p.Arg890Ter Pathogenic ★★ same condition
CNTNAP1 p.Trp672Ter Pathogenic ★★ same condition
CNTNAP1 p.Arg1073His Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Arg1187His Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Arg839Trp Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cntnap1-p-asp109 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown